Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study

• Published in: Drug safety Vol. 45; no. 6; pp. 685 - 698
• Main Authors: Shoaibi, Azza, Rao, Gowtham A., Voss, Erica A., Ostropolets, Anna, Mayer, Miguel Angel, Ramírez-Anguita, Juan Manuel, Maljković, Filip, Carević, Biljana, Horban, Scott, Morales, Daniel R., Duarte-Salles, Talita, Fraboulet, Clement, Le Carrour, Tanguy, Denaxas, Spiros, Papez, Vaclav, John, Luis H., Rijneek, Peter R., Minty, Evan, Alshammari, Thamir M., Makadia, Rupa, Blacketer, Clair, DeFalco, Frank, Sena, Anthony G., Suchard, Marc A., Prieto-Alhambra, Daniel, Ryan, Patrick B.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2022; Springer Nature B.V
• Subjects: Algorithms; Biobanks; Cohort analysis; Cohort Studies; Collaboration; Coronaviruses; COVID-19; COVID-19 vaccines; COVID-19 Vaccines - adverse effects; Data sources; Diagnosis; Drug Safety and Pharmacovigilance; Electronic health records; Electronic medical records; Hematology; Heterogeneity; Hospitals; Humans; Immunization; Informatics; Information systems; Laboratories; Medicine; Medicine & Public Health; Original; Original Research Article; Pandemics; Patients; Pharmacology/Toxicology; Phenotype; Phenotypes; Primary care; Retrospective Studies; Surveillance; Thrombocytopenia; Thrombocytopenia - chemically induced; Thrombocytopenia - epidemiology; Thromboembolism; Thrombosis; Thrombosis - chemically induced; Thrombosis - etiology; Vaccines; Viral diseases; United Kingdom > UK; United States > US; Europe; Japan; Scotland; Australia; Serbia; Germany; Spain
• DOI: 10.1007/s40264-022-01187-y
• EISSN: 1179-1942
• ISSN: 0114-5916

Introduction
Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines.
Objectives
In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients.
Methods
We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data.
Results
Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common.
Conclusion
Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date.